1. Field of the Invention
This invention relates generally to a method for optimizing the administration of leptin receptor ligands to a mammal in need of such treatment. More specifically, this invention relates to an improved method of delivering leptin receptor ligands to a mammal in need of such treatment comprising pulsatile or peak delivery of leptin receptor ligands to treat obesity and related conditions, including hyperglucocorticoidemia, fertility or delayed puberty, and/or growth hormone deficiencies.
2. Description of the Related Art
A diurnal rhythm has been demonstrated with leptin levels peaking near midnight to early morning hours in either lean or obese subjects. Pulsatility has recently been reported to exist in leptin levels with .about.32 pulses/24 hour period (Licino, J. et al. (1996) Periodicity and pulsatility of circulating leptin levels in men. Submitted). This pulsatility suggests some coordinated synthesis and release of leptin by adipose tissue depots, although a mechanism for such coordination is unknown. Increased leptin with prolonged overfeeding may be the result of alterations in fat stores (Kolaczynski, J. W. et al (1996) Response of leptin to short term and prolonged overfeeding in humans. J. Cln. Endo. Metab. Submitted). As a result, leptin levels are altered according to several overlapping biological rhythms. These biorhythms may be key to optimal leptin action as with other hormones, e.g., LHRH, where continual stimulation yields opposite results to pulsatile stimulation.
Since chronic dosing at high levels of receptor agonists can lead to desensitization, it is possible that leptin resistance evolves from chronic hyperleptinemia.